Food Safety and Methemoglobinemia(Blue Baby Syndrome)

Susie Dai, Ph.D.State Hygienic Lab at the University of Iowa

06/04/2019

What is a Foodborne Disease Outbreak?• A foodborne disease outbreak is defined as an

incident in which two or more persons experience a similar illness resulting from the ingestion of a common food.* Foodborne disease outbreaks should be reported to CDC’s Enteric Diseases Epidemiology Branch through the National Outbreak Reporting System (NORS)

* Before 1992, three exceptions existed to this definition; only one case of botulism, marine-toxin intoxication, or chemical intoxication was required to constitute a foodborne disease outbreak if the etiology was confirmed. The definition was changed in 1992 to require two or more cases to constitute an outbreak.

https://www.cdc.gov/foodsafety/outbreaks/investigating-outbreaks/confirming_diagnosis.html

The Situation

• A local ED called the Iowa Poison Center regarding two young children who had been brought in because of “grey-colored skin”

• No recent illness, no ill contacts• HR 150’S, RR 36-40, BP 89/70 • Initial Labs notable for metabolic acidosis

The Situation

• Both children were found to have significantly elevated MetHemoglobin concentrations and were also anemic

• Treatment– Intubation, ventilation, oxygenation – Methylene blue, 1 mg/kg (specific antidote)– Transfusion 1 unit PRBCs– Discharged home on Hospital Day 5

The Case

• Child A• Methemoglobin = 63%• Hb 7.2 g/dL• Extubated Hospital Day 3• Child B• Methemoglobin = 48.9%• Hb 7.4 g/dL• Extubated Hospital Day 2

MetHb 74.4%; Not this case

Photo Courtesy:†Kimberly A. Barker, PharmD, DABAT

The Case

• No pharmaceutical exposures• No known chemical exposures• No known history of G-6-P Dha deficiency• Diet: Goat’s milk, well water, molasses

• Call made to County PH Department

Methemoglobinemia

• Iron in hemoglobin oxidized from 2+ to 3+* Oxidation can hemolysis

• Blood classically has chocolate brown color• Patients cyanotic but not necessarily distressed• Large list of drugs and toxins causing MetHb

https://emedicine.medscape.com/article/204178-overview

MetHb Signs and Symptoms

• Signs and Sx are that of oxygen deprivation– 3-15% Gray skin discoloration, SpO2 of ~85%– 15-20% Cyanosis, chocolate brown blood– 20-50% SOB, HA, fatigue, dizzy, LOC, syncope– 50-70% Increased RR, metabolic acidosis, arrhythmias, seizures,

coma– >70% Death (usually, but not always)

Causes of MetHemoglobinemia

• Pharmaceuticals– * Phenazopyridine, local anesthetics, dapsone, nitrites, nitrates,

chloroquine, etc.• Chemicals / Toxins*

– Nitrite and Nitrate derivatives, perchlorates, chlorites, copper sulfate, naphthalene, etc.

• Hemoglobin M Disease• NADH Cytochrome b5 Reductase Deficiency

– Methmoglobin reductase deficiency

MetHb Treatment: Methylene Blue

• Dose: 1-5 mg / kg* Slow IVP over 5 minutes• Becomes oxidative at 5 mg / kg• Results in blue urine

Event Timeline

Nitrate Detection in Foods- FERN method

• Ion Chromatography• Samples are diluted in water,

then tested• Peaks areas are compared to

known amounts of nitrate

Food Chemistry at SHL• FERN- Food Emergency Response

Network– Funded through FDA– One of 14 state labs throughout the

US that provide surge capacity– Perform testing for a wide variety of

potential contaminants in food

• ISO Accreditation

Sample Results

• Blue = Sample (diluted 1:10)• Black = 1000 ppm (1 mg/mL)

standard

• Final concentration of nitrate in the sorghum syrup ~ 19 mg/mL nitrate per gram of syrup

• Emergency situation Validation—FDA guidance

Spectroscopy

Fourier-transform infrared

Spectroscopy

Raman Spectroscopy

Atomic Absorption Spectroscopy

Inductively coupled plasma atomic

emission spectroscopy

Radiochemistry

Gas-Flow Proportional

Counters

Liquid Scintillation Counters

Alpha Spectrometer

Gamma Spectrophotometer

Chromatography

Gas Chromatography

High Performance Liquid

Chromatography

Mass Spectrometry

Ion Trap

Triple Quadrupole

GC/ICP Mass Spectrometer

SHL Tool Suite

Partnership with local counties

State Hygienic Laboratory

State Hygienic Laboratory

Public Advisory

State Hygienic Laboratory

Acknowledgement

Dr. Edward BotteiDr. Caitlin PedatiSteve MandernachTim WickamJames Lacina